ABSTRACT Overall, 15% of women living with HIV worldwide are aged 15-24 years, with the majority (80%) living in sub- Saharan Africa. Although HIV care and treatment initiatives as well as scale-up of prevention activities have dramatically reduced HIV infection rates in much of sub-Saharan Africa (SSA), young women there experience among the highest HIV incidence rates in the world. Recent research has demonstrated the efficacy of several interventions to reduce risk of HIV in adolescent girls and young women (AGYW) by reducing HIV acquisition in men through male circumcision or reducing transmission from HIV-infected men through early antiretroviral therapy (ART). Interventions for AGYW themselves have included biomedical interventions such as ART- based microbicides or pre-exposure prophylaxis, and social protection interventions including safe spaces, cash transfers for staying in school, life skills training, and community support for changes in gender norms. Because no single biomedical, behavioral or structural intervention is highly effective for AGYW, the most effective approach will likely involve multiple interventions in combination. The success of combination prevention interventions will depend not only on the efficacy of their component parts but also on the feasibility of broad implementation and the acceptability of individual components which, in turn, affect uptake and adherence. One challenge for program implementers is bridging from clinical trials to program implementation since the trial populations are different from the overall population of AGYW ? thus data from trial participants may not predict real-world acceptability and the influence of individual, provider and community attributes on AGYW?s uptake of and adherence to HIV prevention strategies. An additional challenge is programmatic data are usually are not hypothesis-driven, and do not maintain the same research rigor in study design, data collection and annotation, that randomized clinical trials do. Thus, relying on program data alone for multi-level factor analysis is highly likely to produce biased results. In this application, we tackle the challenges of analyzing the influence of multiple factors on AGYW?s uptake and adherence leveraging data from both the DREAMS Initiative program and clinical trials in sub-Saharan African AGYW. Our specific aims are: Aim 1. Determine multi-level individual and community risk factors associated with the PrEP uptake and adherence outcomes among AGYW, using programmatic data from the DREAMS Initiative. Aim 2. Enhance multi-level analysis of the factors identified to influence uptake and adherence by AGYW in Aim 1, leveraging data from both the DREAMS Initiative and the HPTN randomized clinical trials. Aim 3. Predict the influence of the multi-level factors on AGYW uptake and adherence to HIV prevention packages, and assess their population impact. Aim 4. Bridge between the randomized clinical trials and the implementation studies to assess combination prevention intervention packages with better precision for AGYW?s uptake and adherence.